scholarly journals Brain tumor specifies intermediate progenitor cell identity by attenuating  -catenin/Armadillo activity

Development ◽  
2013 ◽  
Vol 141 (1) ◽  
pp. 51-62 ◽  
Author(s):  
H. Komori ◽  
Q. Xiao ◽  
B. M. McCartney ◽  
C.-Y. Lee
Keyword(s):  
Brain Tumor ◽  
Progenitor Cell ◽  
Cell Identity ◽  
Intermediate Progenitor Cell

TAMI-36. TAMEP ARE BRAIN TUMOR PARENCHYMAL CELLS CONTROLLING NEOPLASTIC ANGIOGENESIS AND PROGRESSION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi205-vi206
Author(s):  
Roland Kälin ◽  
Linzhi Cai ◽  
Yuping Li ◽  
Ines Hellmann ◽  
Rainer Glass
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Single Cell ◽  
Disease Progression ◽  
Progenitor Cell ◽  
Local Environment ◽  
Lineage Tracing ◽  
Immunofluorescence Analysis ◽  
Progenitor Cell Population ◽  
Parenchymal Cells

Abstract Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor-parenchymal cells may promote specific phases of disease-progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Strikingly, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell-population, by conditional Sox2-knockout, drastically reduced glioblastoma-vascularization and -size. TAMEP manipulation profoundly altered vessel function and strongly attenuated the blood-tumor barrier. Hence, our data indicate TAMEP and their progenitors as new targets for glioblastoma therapy.

scholarly journals Pax6 Controls Progenitor Cell Identity and Neuronal Fate in Response to Graded Shh Signaling

Cell ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 169-180 ◽  
Author(s):  
J Ericson ◽  
P Rashbass ◽  
A Schedl ◽  
S Brenner-Morton ◽  
A Kawakami ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Shh Signaling ◽  
Cell Identity ◽  
Neuronal Fate

scholarly journals OTME-1. TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii13-ii13
Author(s):  
Roland Kälin ◽  
Linzhi Cai ◽  
Yuping Li ◽  
Louisa von Baumgarten ◽  
Christian Schulz ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Single Cell ◽  
Progenitor Cell ◽  
Local Environment ◽  
Lineage Tracing ◽  
Strong Impact ◽  
Immunofluorescence Analysis ◽  
Progenitor Cell Population ◽  
Parenchymal Cells

Abstract Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression.

Local progenitor cells shape the neoplastic vasculature and promote brain tumor growth.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14044-e14044
Author(s):  
Roland Kälin ◽  
Linzhi Cai ◽  
Dongxu Zhao ◽  
Huabin Zhang ◽  
Wenlong Zhang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Single Cell ◽  
Progenitor Cells ◽  
Cell Population ◽  
Expression Profile ◽  
Progenitor Cell ◽  
Myeloid Cells ◽  
Lineage Tracing

e14044 Background: Aggressive brain tumors like glioblastoma depend on support by their local environment. While the role of tumor-associated myeloid cells on glioblastoma progression is well-documented, we have only partial knowledge of the pathological impact of glioblastoma -parenchymal progenitor cells. Methods: We investigated the glioblastoma microenvironment with transgenic lineage-tracing models ( nestin-creER2, R26-tdTomato and sox2-creER2,R26-tdTomato), intravital imaging, single-cell transcriptomics, immunofluorescence and flow-cytometry as well as histopathology and characterized a previously unknown tumor-associated progenitor cell. In functional experiments, we studied the knockout of the transcription factor SOX2 in these tumor-associated cells. Results: Lineage-traced cells from mouse glioblastoma were obtained by flow-cytometry and single cell transcriptomes compared to established gene expression data from brain tumor parenchymal cells. The traced tumor-associated cells had a transcriptomic profile largely resembling myeloid cells and expressed microglia-/macrophage-markers on the protein-level. However, transgenic models and bone-marrow chimera revealed that the traced cells were clearly distinct from microglia or macrophages. The traced tumor associated cells with a myeloid expression profile derived from a SOX2-dependent progenitor cell. Consequently, conditional Sox2-knockout ablated the entire myeloid-like cell population. Remarkably, this tumor-associated cell population had a large impact on disease-progression causing significant reduction of glioblastoma –vascularization to 53%, changing vascular function and leading to a decrease in tumor volume to 42% as compared to controls. The myeloid-like progenitor cells were identified in human brain tumors by immunofluorescence and in scRNA-seq data. Conclusions: We identified a previously unacknowledged population of tumor-associated progenitor cells with a myeloid-like expression profile that transiently appeared during glioblastoma growth. These progenitors have strong impact on glioblastoma progression and point towards a new and promising therapeutic target in order to support anti-angiogenic regimen in glioblastoma.

In vivo magnetic resonance imaging tracks adult neural progenitor cell targeting of brain tumor

NeuroImage ◽  
2004 ◽  
Vol 23 (1) ◽  
pp. 281-287 ◽  
Author(s):  
Zhenggang Zhang ◽  
Quan Jiang ◽  
Feng Jiang ◽  
Gaungliang Ding ◽  
Ruilan Zhang ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Brain Tumor ◽  
Magnetic Resonance ◽  
Progenitor Cell ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Cell Targeting ◽  
Resonance Imaging

scholarly journals Molecular Profiling Reveals Involvement of ESCO2 in Intermediate Progenitor Cell Maintenance in the Developing Mouse Cortex

2021 ◽  
Author(s):  
Pauline Antonie Ulmke ◽  
M. Sadman Sakib ◽  
Peter Ditte ◽  
Godwin Sokpor ◽  
Cemil Kerimoglu ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Molecular Profiling ◽  
Mouse Cortex ◽  
Intermediate Progenitor Cell ◽  
Cell Maintenance

Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4855-4866 ◽  
Author(s):  
K.F. Liem ◽  
T.M. Jessell ◽  
J. Briscoe
Keyword(s):  
Neural Tube ◽  
Progenitor Cell ◽  
Cell Types ◽  
Neural Cell ◽  
Bmp Signaling ◽  
Neural Cells ◽  
Cell Identity ◽  
Neuronal Fate ◽  
Ventral Neural Tube

The secretion of Sonic hedgehog (Shh) from the notochord and floor plate appears to generate a ventral-to-dorsal gradient of Shh activity that directs progenitor cell identity and neuronal fate in the ventral neural tube. In principle, the establishment of this Shh activity gradient could be achieved through the graded distribution of the Shh protein itself, or could depend on additional cell surface or secreted proteins that modify the response of neural cells to Shh. Cells of the neural plate differentiate from a region of the ectoderm that has recently expressed high levels of BMPs, raising the possibility that prospective ventral neural cells are exposed to residual levels of BMP activity. We have examined whether modulation of the level of BMP signaling regulates neural cell responses to Shh, and thus might contribute to the patterning of cell types in the ventral neural tube. Using an in vitro assay of neural cell differentiation we show that BMP signaling markedly alters neural cell responses to Shh signals, eliciting a ventral-to-dorsal switch in progenitor cell identity and neuronal fate. BMP signaling is regulated by secreted inhibitory factors, including noggin and follistatin, both of which are expressed in or adjacent to the neural plate. Conversely, follistatin but not noggin produces a dorsal-to-ventral switch in progenitor cell identity and neuronal fate in response to Shh both in vitro and in vivo. These results suggest that the specification of ventral neural cell types depends on the integration of Shh and BMP signaling activities. The net level of BMP signaling within neural tissue may be regulated by follistatin and perhaps other BMP inhibitors secreted by mesodermal cell types that flank the ventral neural tube.

scholarly journals A Homeodomain Protein Code Specifies Progenitor Cell Identity and Neuronal Fate in the Ventral Neural Tube

Cell ◽  
2000 ◽  
Vol 101 (4) ◽  
pp. 435-445 ◽  
Author(s):  
James Briscoe ◽  
Alessandra Pierani ◽  
Thomas M Jessell ◽  
Johan Ericson
Keyword(s):  
Neural Tube ◽  
Progenitor Cell ◽  
Homeodomain Protein ◽  
Cell Identity ◽  
Neuronal Fate ◽  
Ventral Neural Tube ◽  
Protein Code
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